A Family-Genetic Study of Pathological Gambling

描述（由申请人提供）：病态赌博（PG）已经成为一个主要的健康问题，特别是随着赌博机会的激增。尽管它很重要，但目前还没有对PG进行直接的家庭访谈研究。本项目的目的是通过盲法和对照家庭研究来探讨PG的家族性。我们计划用DSM-IV PG评估124名受试者和124名匹配的对照（通过随机数字拨号识别），提供全面的表型评估，然后盲目采访他们18岁及以上的一级亲属。先证者和亲属将使用NORC DSM赌博问题筛查（NODS）进行评估；DSM-IV （SCID）的结构化临床访谈；家族史研究诊断标准（FH-RDC），旨在收集家族史的访谈；DSM-IV人格障碍结构化访谈（SIDP-IV）；以及明尼苏达州冲动障碍访谈（MIDI），收集可能与PG相关的其他冲动控制障碍的信息。18岁以下儿童将通过先证者使用儿童行为检查表（CBCL）进行评估。采访者将在这些仪器的管理方面接受充分培训，并将接受认真的培训以实现可靠性，并将每月与PI会面，进行持续培训以确保诊断的可靠性。由于PG经常被认为与情绪障碍、注意缺陷多动障碍、成瘾性障碍和冲动控制障碍有关，并且是强迫症谱系的一部分，我们将对评估这些病症的亲属特别感兴趣。根据原始访谈数据、病例叙述和医疗记录，对每个受试者进行最佳估计诊断。这将导致248名先证者（124名PG， 124名对照）和近1500名亲属（每个先证者组750名）的最佳估计诊断评估。将使用生存曲线、比例风险回归、逻辑回归和线性回归对数据进行完整的分析，以检验研究假设。该研究的主要目的是确定PG是否具有家族性，检查合并症的家族聚集模式，并调查先证和亲属中PG相关的临床特征。次要目标将是检验Blaszczynski的“路径”模型（假设PG的三种不同亚型）的有效性，并验证PG，药物滥用和反社会人格障碍的集合是否像Krueger假设的那样包含一个“外化因素”。这些发现将有助于我们对PG的病因学、病理生理学、分类、亚型和治疗的理解。未来的研究将包括从遗传信息丰富的家族中收集DNA血样进行连锁和关联研究；先证者评估PG病程的随访研究；以及对患有PG的先证者的后代进行后续研究，以检查可能易患PG的早期特征。

DESCRIPTION (provided by applicant): Pathological gambling (PG) has become a major health concern, particularly as gambling opportunities have proliferated. Despite its importance, there are no direct family interview studies of PG. The goal of this project is to explore the familial nature of PG through a blind and controlled family study. We plan to assess 124 subjects with DSM-IV PG and 124 matched controls (identified through random digit dialing), providing a comprehensive phenotypic assessment, and then blindly interviewing their first-degree relatives 18 years and older. Probands and relatives will be assessed using the NORC DSM Screen for Gambling Problems (NODS); the Structured Clinical Interview for DSM-IV (SCID); the Family History Research Diagnostic Criteria (FH-RDC), an interview designed to collect family history; the Structured Interview for DSM-IV Personality Disorder (SIDP-IV); and the Minnesota Impulsive Disorders Interview (MIDI), to collect information on other impulse control disorders that may be related to PG. Children under 18 years will be assessed through the proband with the Child Behavior Checklist (CBCL). Interviewers will be fully trained in the administration of these instruments and will undergo careful training to achieve reliability, and will meet monthly with the PI for ongoing training to ensure diagnostic reliability. Because PG has frequently been considered related to mood disorders, attention deficit hyperactivity disorder, addictive disorders, and impulse control disorders, as well as being part of an obsessive-compulsive spectrum, we will be particularly interested in assessing relatives for these conditions. Best-estimate diagnoses will be made for each subject based on raw interview data, case narratives, and medical records. This should lead to best-estimate diagnostic evaluations for 248 probands (124 PG, 124 control) and nearly 1,500 relatives (750 per proband group). A complete analysis of the data will be performed to test the study hypotheses using survival curves, proportional hazards regression, and both logistic and linear regression. The primary goal of the study is to determine whether PG is familial, to examine the pattern of familial aggregation of comorbid disorders, and to investigate the clinical characteristics associated with PG in probands and relatives. Secondary goals will be to examine the validity of Blaszczynski's "pathways" model (hypothesizing three distinct subtypes of PG), and to verify whether the aggregation of PG, substance misuse, and antisocial personality disorder comprise an "externalizing factor" as hypothesized by Krueger. The findings should add to our understanding of the etiology, pathophysiology, classification, subtyping, and treatment of PG. Future studies will include collecting blood samples for DNA from genetically informative families for linkage and association studies; follow-up studies of probands to assess the course of PG; and follow-up studies of offspring of probands with PG to examine early traits which may predispose to PG.